e16534 Background: The role of oxidative stress in tumor growth and the multifaceted functional significance of glutathione have led to an interest in studying the components of the glutathione-dependent system in gastric cancer (GC), which occupies a leading position in cancer incidence and mortality. The aim of this work was to study the functioning of the glutathione system in the red blood cells of patients with gastric cancer in a comparative aspect depending on the histotype of the tumor and the prevalence of the disease. Methods: The study included 89 patients with GC divided into 6 groups depending on the histotype of the tumor. Separately, the results of the study were analyzed in patients with T4 status according to TNM and in patients with stage IV cancer. The content of reduced glutathione and the activity of glutathione-dependent enzymes were studied by conventional spectrophotometric methods in the red blood cells of patients. Statistical processing of the results was performed using the Statistika 6.0 program with Student’s t-test for two independent groups. Results: An increase in the content of glutathione in patients with GC compared with the group without oncopathology was revealed. The maximum increase was observed in patients with low-grade adenocarcinoma - by 42.5%, while in signet ring cell cancer (SRCC) there was only a tendency to increase by 17.8%. Glutathione reductase activity was reduced in adenocarcinoma by 23.4-26.2% and did not change in SRCC. The activity of the antioxidant enzymes glutathione peroxidase and glutathione transferase was increased in all groups and especially in SRCC - by 76% and 23-29%, respectively. In patients with T4 status and at stage 4 of the process, lower activity of the studied glutathione-dependent enzymes was revealed compared with all other groups of patients. Conclusions: The data indicate a greater functional potential of the glutathione system in SRCC. A significant increase in the activity of glutathione transferase with a sufficiently high level of reduced glutathione contributes to the development of treatment resistance in patients with SRCC.